ood transfusion is generally the process of receiving blood products into one's

circulation intravenously. Transfusions are used for various medical conditions

to replace lost components of the blood. Early transfusions used whole blood, bu
t modern medical practice commonly uses only components of the blood, such as re
d blood cells, white blood cells, plasma, clotting factors, and platelets.
Contents [hide]
1 Medical uses
2 Procedure
2.1 Blood donation
2.2 Processing and testing
2.3 Compatibility testing
3 Adverse effects
3.1 Immunologic reaction
3.2 Infection
3.3 Inefficacy
3.4 Other
4 Frequency of use
5 History
5.1 Early attempts
5.1.1 Animal blood
5.1.2 Human blood
5.2 Modern era
5.2.1 Blood banks in WW1
5.2.2 Expansion
5.2.3 Medical advances
6 Special populations
6.1 Neonate
6.2 Massive trauma
6.3 Unknown blood type
6.4 Religious objections
7 Research into alternatives
8 Veterinary use
9 See also
10 References
11 External links
Medical uses[edit]
Historically, red blood cell transfusion was considered when the hemoglobin leve
l fell below 10 g/dL or hematocrit falls below 30% (the "10/30 rule").[1][2] Bec
ause each unit of blood given carries risks, a trigger level lower than that at
7-8 g/dL is now usually used as it has been shown to have better patient outcome
s.[3] The administration of a single unit of blood is the standard for hospitali
zed people who are not bleeding, with this treatment then followed with re-asses
sment and consideration of symptoms and hemoglobin concentration.[3] Patients wi
th poor oxygen saturation may need more blood.[3] The advisory caution to use bl
ood transfusion only with more severe anemia is in part due to evidence that out
comes are worsened if larger amounts are given.[4] One may consider transfusion
for people with symptoms of cardiovascular disease such as chest pain or shortne
ss of breath.[2] In cases where patients have low levels of hemoglobin but are c
ardiovascularly stable, parenteral iron is a preferred option based on both effi
cacy and safety.[5] Other blood products are given where appropriate, such as cl
otting deficiencies.
Procedure[edit]
Illustration depicting intravenous blood transfusion
Before a blood transfusion is given, there are many steps taken to ensure qualit
y of the blood products, compatibility, and safety to the recipient. In 2012, a
national blood policy was in place in 70% of countries and 62% of countries had
specific legislation that covers the safety and quality of blood transfusion.[6]

Blood donation[edit]
Main article: Blood donation
Blood transfusions typically use sources of blood: one's own (autologous transfu
sion), or someone else's (allogeneic or homologous transfusion). The latter is m
uch more common than the former. Using another's blood must first start with don
ation of blood. Blood is most commonly donated as whole blood intravenously and
collecting it with an anticoagulant. In developed countries, donations are usual
ly anonymous to the recipient, but products in a blood bank are always individua
lly traceable through the whole cycle of donation, testing, separation into comp
onents, storage, and administration to the recipient. This enables management an
d investigation of any suspected transfusion related disease transmission or tra
nsfusion reaction. In developing countries the donor is sometimes specifically r
ecruited by or for the recipient, typically a family member, and the donation oc
curs immediately before the transfusion.
Processing and testing[edit]
photograph of a bag containing one unit of fresh frozen plasma
A bag containing one unit of fresh frozen plasma
Donated blood is usually subjected to processing after it is collected, to make
it suitable for use in specific patient populations. Collected blood is then sep
arated into blood components by centrifugation: red blood cells, plasma, platele
ts, albumin protein, clotting factor concentrates, cryoprecipitate, fibrinogen c
oncentrate, and immunoglobulins (antibodies). Red cells, plasma and platelets ca
n also be donated individually via a more complex process called apheresis.
All donated blood is tested for infections.[citation needed] The current protoco
l tests donated blood for HIV-1, HIV-2, HTLV-1, HTLV-2, Hepatitis B, Hepatitis C
, Syphilis (Treponema pallidum), Chagas disease (Trypanosoma cruzi), and West Ni
le Virus. In addition, platelet products are also tested for bacterial infection
s due to its higher inclination for contamination due to storage at room tempera
ture. Presence of Cytomegalovirus (CMV) is also tested because of risk to certai
n immunocompromised recipients if given, such as those with organ transplant or
HIV. However, not all blood is tested for CMV because only a certain amount of C
MV-negative blood needs to be available to supply patient needs. Other than posi
tivity for CMV, any products tested positive for infections are not used.
All donated blood is also tested for ABO and Rh groups, along with the presence
of any red blood cell antibodies.
Leukoreduction is the removal of white blood cells by filtration. Leukoreduced b
lood products are less likely to cause HLA alloimmunization (development of anti
bodies against specific blood types), febrile non-hemolytic transfusion reaction
, cytomegalovirus infection, and platelet-transfusion refractoriness.
Pathogen Reduction treatment that involves, for example, the addition of ribofla
vin with subsequent exposure to UV light has been shown to be effective in inact
ivating pathogens (viruses, bacteria, parasites and white blood cells) in blood
products.[7][8][9] By inactivating white blood cells in donated blood products,
riboflavin and UV light treatment can also replace gamma-irradiation as a method
to prevent graft-versus-host disease (TA-GvHD).[10][11][12]
Compatibility testing[edit]
Illustration of labeled blood bag.
Main articles: ABO blood group system and Rh blood group system
Before a recipient receives a transfusion, compatibility testing between donor a
nd recipient blood must be done. The first step before a transfusion is given is
to Type and Screen the recipient's blood. Typing of recipient's blood determine
s the ABO and Rh status. The sample is then Screened for any alloantibodies that
may react with donor blood.[13] It takes about 45 minutes to complete (dependin
g on the method used). The blood bank scientist also checks for special requirem
ents of the patient (e.g. need for washed, irradiated or CMV negative blood) and
the history of the patient to see if they have a previously identified antibodi

es and any other serological anomalies;.

A positive screen warrants an antibody panel/investigation to determine if it is
clinically significant. An antibody panel consists of commercially prepared gro
up O red cell suspensions from donors that have been phenotyped for antigens tha
t correspond to commonly encountered and clinically significant alloantibodies.
Donor cells may have homozygous (e.g. K+k-), heterozygous (K+k+) expression or n
o expression of various antigens (K-k-). The phenotypes of all the donor cells b
eing tested are shown in a chart. The patient's serum is tested against the vari
ous donor cells. Based on the reactions of the patient's serum against the donor
cells, a pattern will emerge to confirm the presence of one or more antibodies.
Not all antibodies are clinically significant (i.e. cause transfusion reactions
, HDN, etc.). Once the patient has developed a clinically significant antibody i
t is vital that the patient receive antigen-negative red blood cells to prevent
future transfusion reactions. A direct antiglobulin test (Coombs test) is also p
erformed as part of the antibody investigation.[14]
If there is no antibody present, an immediate spin crossmatch or computer assist
ed crossmatch is performed where the recipient serum and donor rbc are incubated
. In the immediate spin method, two drops of patient serum are tested against a
drop of 3-5% suspension of donor cells in a test tube and spun in a serofuge. Ag
glutination or hemolysis (i.e., positive Coombs test) in the test tube is a posi
tive reaction and the unit should not be transfused.
If an antibody is suspected, potential donor units must first be screened for th
e corresponding antigen by phenotyping them. Antigen negative units are then tes
ted against the patient plasma using an antiglobulin/indirect crossmatch techniq
ue at 37 degrees Celsius to enhance reactivity and make the test easier to read.
In urgent cases where crossmatching cannot be completed, and the risk of droppin
g hemoglobin outweighs the risk transfusing uncrossmatched blood, O-negative blo
od is used, followed by crossmatch as soon as possible. O-negative is also used
for children and women of childbearing age. It is preferable for the laboratory
to obtain a pre-transfusion sample in these cases so a type and screen can be pe
rformed to determine the actual blood group of the patient and to check for allo
antibodies.
Adverse effects[edit]
In the same way that the safety of pharmaceutical products are overseen by pharm
acovigilance, the safety of blood and blood products are overseen by Haemovigila
nce. This is defined by the World Health Organization (WHO) as a system "...to i
dentify and prevent occurrence or recurrence of transfusion related unwanted eve
nts, to increase the safety, efficacy and efficiency of blood transfusion, cover
ing all activities of the transfusion chain from donor to recipient." The system
should include monitoring, identification, reporting, investigation and analysi
s of adverse events near-misses and reactions related to transfusion and manufac
turing.[15] In the UK this data is collected by an independent organisation call
ed SHOT (Serious Hazards Of Transfusion).[16]
Transfusions of blood products are associated with several complications, many o
f which can be grouped as immunological or infectious. There is controversy on p
otential quality degradation during storage.[17]
Immunologic reaction[edit]
This article needs additional citations for verification. Please help improve th
is article by adding citations to reliable sources. Unsourced material may be ch
allenged and removed. (July 2014)
Acute hemolytic reactions occur with transfusion of red blood cells, and occurs
in about 0.016 percent of transfusions, with about 0.003 percent being fatal.[ci

tation needed] This is due to destruction of donor red blood cells by preformed
recipient antibodies. Most often this occurs due to clerical errors or improper
ABO blood typing and crossmatching resulting in a mismatch in ABO blood type bet
ween the donor and the recipient. Symptoms include fever, chills, chest pain, ba
ck pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop i
n blood pressure. When suspected, transfusion should be stopped immediately, and
blood sent for tests to evaluate for presence of hemolysis. Treatment is suppor
tive. Kidney injury may occur due to the effects of the hemolytic reaction (pigm
ent nephropathy).
Delayed hemolytic reactions occur more frequently (about 0.025 percent of transf
usions) and are due to the same mechanism as in acute hemolytic reactions. Howev
er, the consequences are generally mild and a great proportion of patients may n
ot have symptoms. However, evidence of hemolysis and falling hemoglobin levels m
ay still occur. Treatment is generally not needed, but due to the presence of re
cipient antibodies, future compatibility may be affected.
Febrile nonhemolytic reactions are the most common type of blood transfusion rea
ction and occur due to the release of inflammatory chemical signals released by
white blood cells in stored donor blood. This type of reaction occurs in about 7
% of transfusions. Fever is generally short lived and is treated with antipyreti
cs, and transfusions may be finished as long as an acute hemolytic reaction is e
xcluded. This is a reason for the now-widespread use of leukoreduction - the fil
tration of donor white cells from red cell product units.
Allergic reactions may occur when the recipient has preformed antibodies to cert
ain chemicals in the donor blood, and does not require prior exposure to transfu
sions. Symptoms include hives, itching, low blood pressure, and respiratory dist
ress which may lead to anaphylactic shock. Treatment is the same as for any othe
r type 1 hypersensitivity reactions and includes administering intramuscular epi
nephrine, glucocorticoids, antihistamines, medications to keep the blood pressur
e from dropping, and mechanical ventilation if needed. A small population (0.13%
) of patients are deficient in the immunoglobulin IgA, and upon exposure to IgAcontaining blood, may develop an anaphylactic reaction.
Posttransfusion purpura is a rare complication that occurs after transfusion con
taining platelets that express a surface protein HPA-1a. Recipients who lack thi
s protein develop sensitization to this protein from prior transfusions, and dev
elop thrombocytopenia about 7 10 days after subsequent transfusions. Treatment is
with intravenous immunoglobulin, and recipients should only receive future trans
fusions with washed cells or HPA-1a negative cells.
Transfusion-associated acute lung injury (TRALI) is a syndrome of acute respirat
ory distress, often associated with fever, non-cardiogenic pulmonary edema, and
hypotension, which may occur as often as 1 in 2000 transfusions.[18] Symptoms ca
n range from mild to life-threatening, but most patients recover fully within 96
hours, and the mortality rate from this condition is less than 10%.[19] Althoug
h the cause of TRALI is not clear, it has been consistently associated with anti
-HLA antibodies. Because these types of antibodies are commonly formed during pr
egnancy, several transfusion organisations have decided to use only plasma from
men for transfusion.[20] TRALI is typically associated with plasma components ra
ther than packed red blood cells (RBCs), though there is some residual plasma in
RBC units.[20]
Infection[edit]
The use of greater amount of red blood cells is associated with a high risk of i
nfections. In those who were given red blood only with significant anemia infect
ion rates were 12% while in those who were given red blood at milder levels of a
nemia infection rates were 17%.[21]
On rare occasion, blood products are contaminated with bacteria. This can result
in life-threatening infection, also known as transfusion-transmitted bacterial
infection. The risk of severe bacterial infection is estimated, as of 2002, at a
bout 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfus
ions.[22] Blood product contamination, while rare, is still more common than act
ual infection. The reason platelets are more often contaminated than other blood

products is that they are stored at room temperature for short periods of time.
Contamination is also more common with longer duration of storage, especially w
hen exceeding 5 days. Sources of contaminants include the donor's blood, donor's
skin, phlebotomist's skin, and from containers. Contaminating organisms vary gr
eatly, and include skin flora, gut flora, or environmental organisms. There are
many strategies in place at blood donation centers and laboratories to reduce th
e risk of contamination. A definite diagnosis of transfusion-transmitted bacteri
al infection includes the identification of a positive culture in the recipient
(without an alternative diagnosis) as well as the identification of the same org
anism in the donor blood.
Since the advent of HIV testing of donor blood in the 1980s, the transmission of
HIV during transfusion has dropped dramatically. Prior testing of donor blood o
nly included testing for antibodies to HIV. However, due to latent infection (th
e "window period" in which an individual is infectious, but has not had time to
develop antibodies), many cases of HIV seropositive blood were missed. The devel
opment of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rat
e of donor blood seropositivity to about 1 in 3 million units. As transmittance
of HIV does not necessarily mean HIV infection, the latter could still occur, at
an even lower rate.
The transmission of hepatitis C via transfusion currently stands at a rate of ab
out 1 in 2 million units. As with HIV, this low rate has been attributed to the
ability to screen for both antibodies as well as viral RNA nucleic acid testing
in donor blood.
Other rare transmissible infections include hepatitis B, syphilis, Chagas diseas
e, cytomegalovirus infections (in immunocompromised recipients), HTLV, and Babes
ia.
Inefficacy[edit]
Transfusion inefficacy or insufficient efficacy of a given unit(s) of blood prod
uct, while not itself a "complication" per se, can nonetheless indirectly lead t
o complications - in addition to causing a transfusion to fully or partly fail t
o achieve its clinical purpose. This can be especially significant for certain p
atient groups such as critical-care or neonatals.
For red blood cells (RBC), by far the most commonly transfused product, poor tra
nsfusion efficacy can result from units damaged by the so-called storage lesion
- a range of biochemical and biomechanical changes that occur during storage. Wi
th red cells, this can decrease viability and ability for tissue oxygenation.[23
] Although some of the biochemical changes are reversible after the blood is tra
nsfused,[24] the biomechanical changes are less so,[25] and rejuvenation product
s are not yet able to adequately reverse this phenomenon.[26] There has been con
troversy about whether a given product unit's age is a factor in transfusion eff
icacy, specifically about whether "older" blood directly or indirectly increases
risks of complications.[27][28] Studies have not been consistent on answering t
his question,[29] with some showing that older blood is indeed less effective bu
t with others showing no such difference; these developments are being closely f
ollowed by hospital blood bankers - who are the physicians, typically pathologis
ts, who collect and manage inventories of tranfusable blood units.
Certain regulatory measures are in place to minimize RBC storage lesion - includ
ing a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold
(currently 1% in the US, 0.8% in Europe), and a minimum level of post-transfusi
on RBC survival in vivo (currently 75% after 24 hours).[30] However, all of thes
e criteria are applied in a universal manner that does not account for differenc
es among units of product.[31] For example, testing for the post-transfusion RBC
survival in vivo is done on a sample of healthy volunteers, and then compliance
is presumed for all RBC units based on universal (GMP) processing standards (of

course, RBC survival by itself does not guarantee efficacy, but it is a necessa
ry prerequisite for cell function, and hence serves as a regulatory proxy). Opin
ions vary as to the "best" way to determine transfusion efficacy in a patient in
vivo.[32] In general, there are not yet any in vitro tests to assess quality or
predict efficacy for specific units of RBC blood product prior to their transfu
sion, though there is exploration of potentially relevant tests based on RBC mem
brane properties such as erythrocyte deformability[33] and erythrocyte fragility
(mechanical).[34]
Physicians have adopted a so-called "restrictive protocol" - whereby transfusion
is held to a minimum - due in part to the noted uncertainties surrounding stora
ge lesion, in addition to the very high direct and indirect costs of transfusion
s.[35][36][37] Of course, restrictive protocol is not an option with some especi
ally vulnerable patients who may require the best possible efforts to rapidly re
store tissue oxygenation.
Although tranfusions of platelets are far less numerous (relative to RBC), plate
let storage lesion and resulting efficacy loss is also a concern.[38]
Other[edit]
A known relationship between intra-operative blood transfusion and cancer recurr
ence has been established in colorectal cancer.[39] In lung cancer intra-operati
ve blood transfusion has been associated with earlier recurrence of cancer, wors
e survival rates and poorer outcomes after lung resection.[40][41]
Transfusion-associated volume overload is a common complication simply due to th
e fact that blood products have a certain amount of volume. This is especially t
he case in recipients with underlying cardiac or kidney disease. Red cell transf
usions can lead to volume overload when they must be repeated due to insufficien
t efficacy (see above). Plasma transfusion is especially prone to causing volume
overload due to its hypertonicity.
Hypothermia can occur with transfusions with large quantities of blood products
which normally are stored at cold temperatures. Core body temperature can go dow
n as low as 32 C and can produce physiologic disturbances. Prevention should be d
one with warming the blood to ambient temperature prior to transfusions.
Transfusions with large amounts of red blood cells, whether due to severe hemorr
haging and/or transfusion inefficacy (see above), can lead to an inclination for
bleeding. The mechanism is thought to be due to disseminated intravascular coag
ulation, along with dilution of recipient platelets and coagulation factors. Clo
se monitoring and transfusions with platelets and plasma is indicated when neces
sary.
Metabolic alkalosis can occur with massive blood transfusions due to the breakdo
wn of citrate stored in blood into bicarbonate.
Hypocalcemia can also occur with massive blood transfusions due to the complex o
f citrate with serum calcium.
Blood doping is often used by athletes, drug addicts or military personnel for r
easons such as to increase physical stamina, to fake a drug detection test or si
mply to remain active and alert during the duty-times respectively. However a la
ck of knowledge and insufficient experience can turn a blood transfusion into a
sudden death. For example, when individuals run the frozen blood sample directly
in their veins this cold blood rapidly reaches the heart, where it disturbs the
heart's original pace leading to cardiac arrest and sudden death.
Frequency of use[edit]
Globally around 85 million units of red blood cells are transfused in a given ye
ar.[2]
In the United States, blood transfusions were performed nearly 3 million times d
uring hospitalizations in 2011, making it the most common procedure performed. T
he rate of hospitalizations with a blood transfusion nearly doubled from 1997, f
rom a rate of 40 stays to 95 stays per 10,000 population. It was the most common
procedure performed for patients 45 years of age and older in 2011, and among t

he top five most common for patients between the ages of 1 and 44 years.[42]
According to the New York Times: "Changes in medicine have eliminated the need f
or millions of blood transfusions, which is good news for patients getting proce
dures like coronary bypasses and other procedures that once required a lot of bl
ood." And, "Blood bank revenue is falling, and the decline may reach $1.5 billio
n a year this year [2014] from a high of $5 billion in 2008." Job losses will re
ach as high as 12,000 within the next three to five years, roughly a quarter of
the total in the industry, according to the Red Cross.[43]
History[edit]
Beginning with William Harvey's experiments on the circulation of blood, researc
h into blood transfusion began in the 17th century, with successful experiments
in transfusion between animals. However, successive attempts by physicians to tr
ansfuse animal blood into humans gave variable, often fatal, results.
Pope Innocent VIII is sometimes said to have been given the world's first blood
transfusion by his Jewish physician Giacomo di San Genesio, who had him drink (b
y mouth) the blood of three 10-year-old boys. The boys subsequently died. The ev
idence for this story, however, is unreliable and may have been motivated by ant
i-semitism.[44]
Early attempts[edit]
Animal blood[edit]
Richard Lower pioneered the first blood transfusion from animal to human in 1665
at the Royal Society.
Working at the Royal Society in the 1660s, the physician Richard Lower began exa
mining the effects of changes in blood volume on circulatory function and develo
ped methods for cross-circulatory study in animals, obviating clotting by closed
arteriovenous connections. The new instruments he was able to devise enabled hi
m to perform the first reliably documented successful transfusion of blood in fr
ont of his distinguished colleagues from the Royal Society.
According to Lower's account, "...towards the end of February 1665 [I] selected
one dog of medium size, opened its jugular vein, and drew off blood, until ... i
ts strength was nearly gone. Then, to make up for the great loss of this dog by
the blood of a second, I introduced blood from the cervical artery of a fairly l
arge mastiff, which had been fastened alongside the first, until this latter ani
mal showed ... it was overfilled ... by the inflowing blood." After he "sewed up
the jugular veins," the animal recovered "with no sign of discomfort or of disp
leasure."
Lower had performed the first blood transfusion between animals. He was then "re
quested by the Honorable [Robert] Boyle ... to acquaint the Royal Society with t
he procedure for the whole experiment," which he did in December 1665 in the Soc
iety's Philosophical Transactions. [45]
The first blood transfusion from animal to human was administered by Dr. Jean-Ba
ptiste Denys, eminent physician to King Louis XIV of France, on June 15, 1667.[4
6] He transfused the blood of a sheep into a 15-year-old boy, who survived the t
ransfusion.[47] Denys performed another transfusion into a labourer, who also su
rvived. Both instances were likely due to the small amount of blood that was act
ually transfused into these people. This allowed them to withstand the allergic
reaction.
Denys' third patient to undergo a blood transfusion was Swedish Baron Gustaf Bon
de. He received two transfusions. After the second transfusion Bonde died.[48] I
n the winter of 1667, Denys performed several transfusions on Antoine Mauroy wit
h calf's blood, who on the third account died.[49]

Six months later in London, Lower performed the first human transfusion of anima
l blood in Britain, where he "superintended the introduction in [a patient's] ar
m at various times of some ounces of sheep's blood at a meeting of the Royal Soc
iety, and without any inconvenience to him." The recipient was Arthur Coga, "the
subject of a harmless form of insanity." Sheep's blood was used because of spec
ulation about the value of blood exchange between species; it had been suggested
that blood from a gentle lamb might quiet the tempestuous spirit of an agitated
person and that the shy might be made outgoing by blood from more sociable crea
tures. Coga received 20 shillings to participate in the experiment.[50]
Lower went on to pioneer new devices for the precise control of blood flow and t
he transfusion of blood; his designs were substantially the same as modern syrin
ges and catheters.[45] Shortly after, Lower moved to London, where his growing p
ractice soon led him to abandon research.[51]
These early experiments with animal blood provoked a heated controversy in Brita
in and France.[48] Finally, in 1668, the Royal Society and the French government
both banned the procedure. The Vatican condemned these experiments in 1670. Blo
od transfusions fell into obscurity for the next 150 years.
Human blood[edit]
James Blundell, successfully transfused human blood in 1818.
The science of blood transfusion dates to the first decade of the 20th century,
with the discovery of distinct blood types leading to the practice of mixing som
e blood from the donor and the receiver before the transfusion (an early form of
cross-matching).
In the early 19th century, British obstetrician Dr. James Blundell made efforts
to treat hemorrhage by transfusion of human blood using a syringe. In 1818 follo
wing experiments with animals, he performed the first successful transfusion of
human blood to treat postpartum hemorrhage. Blundell used the patient's husband
as a donor, and extracted four ounces of blood from his arm to transfuse into hi
s wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five
of which were beneficial, and published his results. He also invented a number
of instruments for the transfusion of blood.[52] He made a substantial amount of
money from this endeavour, roughly $2 million ($50 million real dollars).[citat
ion needed]
In 1840, at St George's Hospital Medical School in London, Samuel Armstrong Lane
, aided by Dr. Blundell, performed the first successful whole blood transfusion
to treat haemophilia.
However, early transfusions were risky and many resulted in the death of the pat
ient. By the late 19th century, blood transfusion was regarded as a risky and du
bious procedure, and was largely shunned by the medical establishment.
Modern era[edit]
It was not until 1901, when the Austrian Karl Landsteiner discovered three human
blood groups (O, A, and B), that blood transfusion was put onto a scientific ba
sis and became safer.
Mixing blood from two incompatible individuals can lead to an immune response, a
nd the destruction of red blood cells releases free hemoglobin into the bloodstr
eam, which can have fatal consequences. Karl Landsteiner discovered that when in
compatible types are mixed, the red blood cells clump, and that this immunologic
al reaction occurs when the receiver of a blood transfusion has antibodies again
st the donor blood cells. His work made it possible to determine blood type and
allowed a way for blood transfusions to be carried out much more safely. For thi

s discovery he was awarded the Nobel Prize in Physiology and Medicine in 1930, a
nd many other blood groups have been discovered since.
George Washington Crile is credited with performing the first surgery using a di
rect blood transfusion in 1906 at St. Alexis Hospital in Cleveland while a profe
ssor of surgery at Case Western Reserve University.[when?][53]
Jan Jansk also discovered the human blood groups in 1907 which he classified bloo
d into four groups I, II, III, IV. Titled in Czech "Hematologick studie u psychot
iku". His nomenclature is still used in Russia and states of the former USSR, in
which blood types O, A, B, and AB are respectively designated I, II, III, and I
V.
Dr. William Lorenzo Moss's (1876-1957) Moss-blood typing technique of 1910 was w
idely used until World War II.[54][55]
Blood banks in WW1[edit]
Main article: Blood bank
Dr. Luis Agote (2nd from right) overseeing one of the first safe and effective b
lood transfusions in 1914
While the first transfusions had to be made directly from donor to receiver befo
re coagulation, it was discovered that by adding anticoagulant and refrigerating
the blood it was possible to store it for some days, thus opening the way for t
he development of blood banks. John Braxton Hicks was the first to experiment wi
th chemical methods to prevent the coagulation of blood at St Mary's Hospital, L
ondon in the late 19th century. His attempts, using phosphate of soda, however,
were unsuccessful.
The first non-direct transfusion was performed on March 27, 1914 by the Belgian
doctor Albert Hustin, though this was a diluted solution of blood. The Argentine
doctor Luis Agote used a much less diluted solution in November of the same yea
r. Both used sodium citrate as an anticoagulant.[56]
The First World War acted as a catalyst for the rapid development of blood banks
and transfusion techniques. Canadian Lieutenant Lawrence Bruce Robertson was in
strumental in persuading the Royal Army Medical Corps to adopt the use of blood
tranfusion at the Casualty Clearing Stations for the wounded. In October 1915, R
obertson performed his first wartime transfusion with a syringe to a patient suf
fering from multiple shrapnel wounds. He followed this up with four subsequent t
ransfusions in the following months and his success was reported to Sir Walter M
orley Fletcher, director of the Medical Research Committee.
World War II Russian syringe for direct inter-human blood transfusion.
Robertson published his findings in the British Medical Journal in 1916 and, wit
h the help of a few like minded individuals (including the eminent physician Edw
ard William Archibald who introduced the citrate anticoagulant method), was able
to persuade the British authorities of the merits of blood transfusion. Roberts
on went on to establish the first blood transfusion apparatus at a Casualty Clea
ring Station on the Western Front in the spring of 1917. [57]
Oswald Hope Robertson, a medical researcher and U.S. Army officer was attached t
o the RAMC in 1917, where he was instrumental in establishing the first blood ba
nks, in preparation for the anticipated Third Battle of Ypres.[58] He used sodiu
m citrate as the anticoagulant and the blood was extracted from punctures in the
vein and was stored in bottles at British and American Casualty Clearing Statio
ns along the Front. He also experimented with preserving separated red blood cel
ls in iced bottles.[57] Geoffrey Keynes, a British surgeon, developed a portable
machine that could store blood to enable transfusions to be carried out more ea

sily.
Expansion[edit]
Alexander Bogdanov established a scientific institute to research the effects of
blood transfusion in Moscow, 1925.
The world's first blood donor service was established in 1921 by the secretary o
f the British Red Cross, Percy Oliver. In that year, Oliver was contacted by Kin
g's College Hospital, where they were in urgent need of a blood donor. [59] Afte
r providing a donor, Oliver set about organizing a system for the voluntary regi
stration of blood donors at clinics around London, with Sir Geoffrey Keynes appo
inted as a medical adviser. Volunteers were subjected to a series of physical te
sts to establish their blood group. The London Blood Transfusion Service was fre
e of charge and expanded rapidly in its first few years of operation. By 1925, i
t was providing services for almost 500 patients and it was incorporated into th
e structure of the British Red Cross in 1926. Similar systems were established i
n other cities including Sheffield, Manchester and Norwich, and the service's wo
rk began to attract international attention. Similar services were established i
n France, Germany, Austria, Belgium, Australia and Japan.[60]
An academic institution devoted to the science of blood transfusion was founded
by Alexander Bogdanov in Moscow in 1925. Bogdanov was motivated, at least in par
t, by a search for eternal youth, and remarked with satisfaction on the improvem
ent of his eyesight, suspension of balding, and other positive symptoms after re
ceiving 11 transfusions of whole blood. Bogdanov died in 1928 as a result of one
of his experiments, when the blood of a student suffering from malaria and tube
rculosis was given to him in a transfusion.[61] Following Bogdanov's lead, Vladi
mir Shamov and Sergei Yudin in the USSR pioneered the transfusion of cadaveric b
lood from recently deceased donors. Yudin performed such a transfusion successfu
lly for the first time on March 23, 1930 and reported his first seven clinical t
ransfusions with cadaveric blood at the Fourth Congress of Ukrainian Surgeons at
Kharkiv in September. However, this method was never used widely, even in Russi
a.
British poster encouraging people to donate blood for the war effort.
One of the earliest blood banks was established by Frederic Durn-Jord during the S
panish Civil War in 1936. Duran joined the Transfusion Service at the Barcelona
Hospital at the start of the conflict, but the hospital was soon overwhelmed by
the demand for blood and the paucity of available donors. With support from the
Department of Health of the Spanish Republican Army, Duran established a blood b
ank for the use of wounded soldiers and civilians. The 300-400 ml of extracted b
lood was mixed with 10% citrate solution in a modified Duran Erlenmeyer flask. T
he blood was stored in a sterile glass enclosed under pressure at 2 C. During 30
months of work, the Transfusion Service of Barcelona registered almost 30,000 do
nors, and processed 9,000 liters of blood. [62]
In 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in
Chicago, established the first hospital blood bank in the United States. In crea
ting a hospital laboratory that preserved, refrigerated and stored donor blood,
Fantus originated the term "blood bank". Within a few years, hospital and commun
ity blood banks were established across the United States.[63]
Frederic Durn-Jord fled to Britain in 1938, and worked with Dr Janet Vaughan at th
e Royal Postgraduate Medical School at Hammersmith Hospital to create a system o
f national blood banks in London.[64] With the outbreak of war looking imminent
in 1938, the War Office created the Army Blood Supply Depot (ABSD) in Bristol he
aded by Lionel Whitby and in control of four large blood depots around the count
ry. British policy through the war was to supply military personnel with blood f
rom centralized depots, in contrast to the approach taken by the Americans and G

ermans where troops at the front were bled to provide required blood. The Britis
h method proved to be more successful at adequately meeting all requirements and
over 700,000 donors were bled over the course of the war. This system evolved i
nto the National Blood Transfusion Service established in 1946, the first nation
al service to be implemented. [65]
Medical advances[edit]
Wounded soldier is given blood plasma in Sicily, 1943.
A blood collection program was initiated in the US in 1940 and Edwin Cohn pionee
red the process of blood fractionation. He worked out the techniques for isolati
ng the serum albumin fraction of blood plasma, which is essential for maintainin
g the osmotic pressure in the blood vessels, preventing their collapse.
The use of blood plasma as a substitute for whole blood and for transfusion purp
oses was proposed as early as 1918, in the correspondence columns of the British
Medical Journal, by Gordon R. Ward. At the onset of World War II, liquid plasma
was used in Britain. A large project, known as 'Blood for Britain' began in Aug
ust 1940 to collect blood in New York City hospitals for the export of plasma to
Britain. A dried plasma package was developed, which reduced breakage and made
the transportation, packaging, and storage much simpler.[66]
Charles R. Drew oversaw the production of blood plasma for shipping to Britain d
uring WW2.
The resulting dried plasma package came in two tin cans containing 400 cc bottle
s. One bottle contained enough distilled water to reconstitute the dried plasma
contained within the other bottle. In about three minutes, the plasma would be r
eady to use and could stay fresh for around four hours.[67] Dr. Charles R. Drew
was appointed medical supervisor, and he was able to transform the test tube met
hods into the first successful technique for mass production.
Another important breakthrough came in 1939-40 when Karl Landsteiner, Alex Wiene
r, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, whi
ch was found to be the cause of the majority of transfusion reactions up to that
time. Three years later, the introduction by J.F. Loutit and Patrick L. Molliso
n of acid-citrate-dextrose (ACD) solution, which reduced the volume of anticoagu
lant, permitted transfusions of greater volumes of blood and allowed longer term
storage.
Carl Walter and W.P. Murphy, Jr. introduced the plastic bag for blood collection
in 1950. Replacing breakable glass bottles with durable plastic bags allowed fo
r the evolution of a collection system capable of safe and easy preparation of m
ultiple blood components from a single unit of whole blood.
In the field of cancer surgery replacement of massive blood loss became a major
problem. The cardiac arrest rate was high. In 1963, C. Paul Boyan and William S.
Howland discovered that the temperature of the blood and the rate of infusion g
reatly affected survival rates, and introduced blood warming to surgery.[68][69]
Further extending the shelf life of stored blood was an anticoagulant preservati
ve, CPDA-1, introduced in 1979, which increased the blood supply and facilitated
resource-sharing among blood banks.
As of 2006, there were about 15 million units of blood products transfused per y
ear in the United States.[70] By 2013, the number had declined to about 11 milli
on units, due to the shift towards laparoscopic surgery and other surgical advan
ces and studies that have shown that many transfusions were unnecessary. For exa
mple, the standard of care reduced that amount of blood transfused from 750 to 2
00 ml.[71]

Special populations[edit]
Neonate[edit]
To ensure the safety of blood transfusion to pediatric patients, hospitals are t
aking additional precaution to avoid infection and prefer to use specially teste
d pediatric blood units that are guaranteed negative for Cytomegalovirus. Most g
uidelines recommend the provision of CMV-negative blood components and not simpl
y leukoreduced components for newborns or low birthweight infants in whom the im
mune system is not fully developed.[72] These specific requirements place additi
onal restrictions on blood donors who can donate for neonatal use. vnv Neonatal
transfusions typically fall into one of two categories:
"Top-up" transfusions, to replace losses due to investigational losses and corre
ction of anemia.
Exchange (or partial exchange) transfusions are done for removal of bilirubin, r
emoval of antibodies and replacement of red cells (e.g., for anemia secondary to
thalassemias and other hemoglobinopathies).[73]
Massive trauma[edit]
A massive transfusion protocol is used for massive trauma resuscitation, when mo
re than ten units of blood are needed. Packed red blood cells, fresh frozen plas
ma, and platelets are administered in lieu of crystalloids or whole blood.[74] T
ypically higher ratios of fresh frozen plasma and platelets are given relative t
o packed red blood cells.[74]
Unknown blood type[edit]
Because blood type O negative is compatible with anyone, it is often overused an
d in short supply.[75] According to the American Association of Blood Banks, the
use of this blood should be restricted to persons with O negative blood, as not
hing else is compatible with them, and women who might be pregnant and for whom
it would be impossible to do blood group testing before giving them emergency tr
eatment.[75] Whenever possible, the AABB recommends that O negative blood be con
served by using blood type testing to identify a less scarce alternative.[75]
Religious objections[edit]
See also: Jehovah's Witnesses and blood transfusions
Objections to blood transfusions may arise for personal, medical, or religious r
easons. For example, Jehovah's Witnesses object to blood transfusion primarily o
n religious grounds they believe that blood is sacred, as the Bible says "abstain
from blood" (Acts 15:28,29). They have also highlighted complications associated
with transfusion.[76]
Research into alternatives[edit]
See also: Blood substitutes
Although there are clinical situations where transfusion with red blood cells is
the only clinically appropriate option, clinicians look at whether alternatives
as feasible. This can be due to several reasons, such as patient safety, econom
ic burden or scarcity of blood. Guidelines recommend blood transfusions should b
e reserved for patients with or at risk of cardiovascular instability due to the
degree of their anaemia.[77][78] In these cases parenteral iron is recommended.
Thus far, there are no available oxygen-carrying blood substitutes, which is the
typical objective of a blood (RBC) transfusion; however, there are widely avail
able non-blood volume expanders for cases where only volume restoration is requi
red. These are helping doctors and surgeons avoid the risks of disease transmiss
ion and immune suppression, address the chronic blood donor shortage, and addres
s the concerns of Jehovah's Witnesses and others who have religious objections t
o receiving transfused blood.
A number of blood substitutes have been explored (and still are), but thus far t
hey all suffer from many challenges. Most attempts to find a suitable alternativ

e to blood thus far have concentrated on cell-free hemoglobin solutions. Blood s

ubstitutes could make transfusions more readily available in emergency medicine
and in pre-hospital EMS care. If successful, such a blood substitute could save
many lives, particularly in trauma where massive blood loss results. Hemopure, a
hemoglobin-based therapy, is approved for use in South Africa.
Veterinary use[edit]
Main article: Blood type (non-human)
Veterinarians also administer transfusions to other animals. Various species req
uire different levels of testing to ensure a compatible match. For example, cats
have 3 known blood types, cattle have 11, dogs have 12, pigs 16 and horses have
34. However, in many species (especially horses and dogs), cross matching is no
t required before the first transfusion, as antibodies against non-self cell sur
face antigens are not expressed constitutively - i.e. the animal has to be sensi
tized before it will mount an immune response against the transfused blood.
The rare and experimental practice of inter-species blood transfusions is a form
of xenograft